TRMT10C agonist TM3 is a small molecule agonist of tRNA methyltransferase 10C (TRMT10C), exhibits direct binding with a dissociation constant (Kd) of 2.6 uM in SPR assays, promotes osteoblast differentiation and protects against osteoporosis.
TM3 (10 nM) promotes OXPHOS subunit expression (including ND1-ND6, CYTB, COX1-COX3, ATP6, and ATP8) in BMSCs.
TM3 significantly stabilized the TRMT10C protein against thermal denaturation in BMSCs by cellular thermal shift assays (CETSA), indicating direct intracellular target engagement.
TM3 enhanced osteogenic differentiation in human BMSCs, but not in the BMSCs derived from the Osx-Cre;Trmt10cfl/fl mice.
TM3 (50 µg/kg/day, i.p.) significantly increased the expression levels of m1A and OXPHOS subunits in bone tissue from welve-week-old C57BL/6 wild-type female mice.
TM3 significantly increased trabecular bone mass and bone mineral density in both the sham-operated and OVX mice.
TM3 significantly increased the levels of the bone formation marker PINP and the bone resorption markers CTX-1 and ACP5 in both the sham and OVX mice, significantly increased dynamic histomorphometric parameters, including the MAR, MS/BS, and BFR/BS.
TM3 (50 μg/kg/day, i.p.) effectively promotes bone formation and protects against bone loss in both estrogen-deficient and aged murine models of osteoporosis.